Developing in vitro patient derived CERvical Cancer OrganoidS (CERCOS) as a potential preclinical tool in cervical cancer research

Abstract

Advanced cervical cancer remains a major cause of mortality in women worldwide as it has limited treatment options and recurrence is very common. This highlights the necessity to develop patient derived organoids (PDOs) as preclinical models, that can recapitulate the clinical heterogeneity of the cancer in terms of molecular features, and genetic background. The PDOs have potential for guiding personalized treatment in clinical practice. In this study, we have established patient-derived cervical cancer organoids or CERvical Cancer OrganoidS (CERCOS) from biopsy samples of five patients having two different subtypes (squamous cell carcinoma and adenocarcinoma) using a modified protocol. The CERCOS were characterized to assess their genetic and phenotypic similarity with the parent tissue. The organoids developed in vitro showed preservation of the histopathological and somatic mutational profile of the parent tissue. Expression of cervical cancer-related genes, including PIK3CA, MET, and LRP1B, was found to be comparable between the organoids and the parent tissue. Moreover, characterization of the PDOs post cryopreservation showed the maintenance of the morphological and histopathological features of the parent tissue. This study demonstrates that the CERvical Cancer OrganoidS (CERCOS), established using the current protocol, preserves genetic and phenotypic similarity and can serve as a platform for precision medicine and biobanking purposes.